Details of Drug Interaction

Details of Drug-Drug Interaction

 Drug General Information (ID: DDIUDQZOKB)
  Drug Name St. John's Wort Drug Info Brivaracetam Drug Info
  Drug Type Natural product Small molecule
  Therapeutic Class Herbal Products/Antidepressants Anticonvulsants

 Mechanism of St. John's Wort-Brivaracetam Interaction (Severity Level: Moderate)
     CYP450 enzyme induction Click to Show/Hide Mechanism Graph
Could Not Find 2D Structure
      Drug Name St. John's Wort Brivaracetam
      Mechanism CYP450 2C19 inducer CYP450 2C19 substrate
      Key Mechanism Factor 1
Factor Name Cytochrome P450 2C19
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Structure Sequence
MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDVSKSLTNLSKIYGPVFTLYFGLERMVVLHGYEVVKEALIDLGEEFSGRGHFPLAERANRGFGIVFSNGKRWKEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICSIIFQKRFDYKDQQFLNLMEKLNENIRIVSTPWIQICNNFPTIIDYFPGTHNKLLKNLAFMESDILEKVKEHQESMDINNPRDFIDCFLIKMEKEKQNQQSEFTIENLVITAADLLGAGTETTSTTLRYALLLLLKHPEVTAKVQEEIERVIGRNRSPCMQDRGHMPYTDAVVHEVQRYIDLIPTSLPHAVTCDVKFRNYLIPKGTTILTSLTSVLHDNKEFPNPEMFDPRHFLDEGGNFKKSNYFMPFSAGKRICVGEGLARMELFLFLTFILQNFNLKSLIDPKDLDTTPVVNGFASVPPFYQLCFIPV
Gene Name CYP2C19
Uniprot ID CP2CJ_HUMAN
KEGG Pathway hsa:1557
Protein Family Cytochrome P450 family
Protein Function
A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:20972997, PubMed:19965576). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307).
    Click to Show/Hide
      Mechanism Description
  • Increased metabolism of Brivaracetam caused by St. John's Wort mediated induction of CYP450 enzyme

Recommended Action
      Management The potential for diminished pharmacologic effects of brivaracetam should be considered during coadministration with potent CYP450 enzyme inducers. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever a CYP450 inducer is added to or withdrawn from therapy. For patients receiving concomitant carbamazepine or phenytoin therapy, blood levels should be monitored following initiation or discontinuation of brivaracetam. Dosage reductions for carbamazepine and phenytoin may be required if tolerability issues arise.

References
1 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
2 Product Information. Briviact (brivaracetam). UCB Pharma Inc, Smyrna, GA.
3 Stockis A, Chanteux H, Rosa M, Rolan P "Brivaracetam and carbamazepine interaction in healthy subjects and in vitro." Epilepsy Res 113 (2015): 19-27. [PMID: 25986188]